rs587776833
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4_SupportingPP5_Moderate
The NM_182925.5(FLT4):c.3323_3325del(p.Phe1108del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
FLT4
NM_182925.5 inframe_deletion
NM_182925.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.30
Genes affected
FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_182925.5. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 5-180614073-GAGA-G is Pathogenic according to our data. Variant chr5-180614073-GAGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 16268.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-180614073-GAGA-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLT4 | NM_182925.5 | c.3323_3325del | p.Phe1108del | inframe_deletion | 24/30 | ENST00000261937.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLT4 | ENST00000261937.11 | c.3323_3325del | p.Phe1108del | inframe_deletion | 24/30 | 1 | NM_182925.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457460Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 725344
GnomAD4 exome
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725344
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital | Jun 11, 2021 | This variant has been previously reported in the scientific literature in association with Milroy disease and primary lymphedemas (PMID: 12960217, PMID: 23074044, PMID: 19002718). - |
Hereditary lymphedema type I Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2003 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at